Broadly conceived, my research objectives are to understand the relationship between the internal environment and behavior. Changes in the milieu interieur of an animal evoke certain behaviors (e.g., increases in blood osmotic pressure are followed by antidiuresis and drinking of water), behaviors which are regulatory in that they accomplish a return to a more or less homeostatic condition. The neural mechanisms which sense changes in the blood or other body fluids are of specific interest to me. Such internal sensing systems must be capable of tranducing physiochemical fluctuations into some kind of cellular response, be it electrical, hormonal or both. The output of these internal "sense organs" must then be integrated into a directed behavior, appropriate to the prevailing circumstances. It is, however, the detectors of the imbalance which initiate the chain of events, and about which we know so little. The methods I am using to investigate these internal sensing systems include analyses of changes in blood volume, blood osmotic pressure, sodium, potassium, protein, and corticosterone; also bioassay of antidiuretic hormone. My attack on the central nervous components of these systems include unit and multiunit recording, lesioning, stimulating, and since our discovery of the nucleolar response as an indicator of metabolic activity, neuroanatomical methods. No single one of these methods provides unequivocal answers to the questions being investigated.